Comparison of the anti-inflammatory and antilipidemic activity of diosmin and saroglitazar in a model of nonalcoholic fatty liver induced by a high-fat diet in Wistar rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 14، دوره 27، شماره 2، اردیبهشت 2024، صفحه 241-246 اصل مقاله (554.39 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.70157.15255 | ||
| نویسندگان | ||
| Reza Afarin1؛ Negar Dinarvand1؛ Bahar Jaberian Asl1؛ Ghazal Orak1؛ Elham Shakerian1؛ Fatemeh Bineshfar2؛ Akram Ahangarpour* 3 | ||
| 1Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | ||
| 2Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | ||
| 3Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | ||
| چکیده | ||
| Objective(s): Non-alcoholic fatty liver disease (NAFLD) is the most common liver-related metabolic disorder in the world, with a global prevalence of 25%. Compounds with anti-inflammatory, lipid-lowering, and insulin-sensitizing properties can be used for the prevention or treatment of NAFLD. Therefore, this study was conducted to investigate the effect of saroglitazar (a dual PPARα/γ agonist) and diosmin (a flavonoid) on non-alcoholic fatty liver induced by a high-fat diet (HFD) in Wistar rats. Materials and Methods: Forty male Wistar rats (6–8 weeks old) were fed an HFD to induce NAFLD. After 7 weeks, rats were divided into four groups: group1 was fed HFD, and the other groups received HFD+saroglitazar, HFD+diosmin, and HFD+ saroglitazar+diosmin. We examined body and liver weight, histopathology, serum levels of liver enzymes (ALT and AST), and lipid profiles (LDL-C and HDL-C) using the standard protocols. qRT-PCR was also used to examine the expression of PPARα, PPARγ, SREBP1c, FAS, ACC, CPT1α, and pro-inflammatory genes (IL6, TNFα, and TGFβ). Results: Rats fed the HFD showed characteristics of NAFLD (pathologically and biochemically). Administration of saroglitazar and diosmin alone caused a significant decrease in the levels of PPARγ, SREBP1c, FAS, ACC, ALT, AST, LDL-C, and pro-inflammatory genes and a significant increase in PPARα, CPT1a, and HDL-C in comparison with the HF group (P<0.05). Their combined effect was more evident. Conclusion: Our results showed that diosmin, like saroglitazar, significantly ameliorated inflammatory and lipid profiles in HFD-induced NAFLD, suggesting that diosmin, as a natural compound, could be a suitable alternative to saroglitazar. | ||
| کلیدواژهها | ||
| Diosmin؛ Non-alcoholic fatty liver disease؛ Non-alcoholic steatohepatitis؛ Saroglitazar؛ TGFβ | ||
| مراجع | ||
|
1. Zhang H, Zhang E, Hu H. Role of ferroptosis in non-alcoholic fatty liver disease and its implications for therapeutic strategies. Biomedicines 2021; 9:1660-1665. 2. Gerges SH, Wahdan SA, Elsherbiny DA, El-Demerdash E. Diosmin ameliorates inflammation, insulin resistance, and fibrosis in an experimental model of non-alcoholic steatohepatitis in rats. Toxicol Appl Pharmacol 2020; 401:115-101. 3. Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, Kassir R, Singhal R, Mahawar K, Ramnarain D. Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord 2022; 22:63-65. 4. Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M, Azarbayjani MA. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. Eur J Sport Sci 2019: 994-1003. 5. Wagner N, Wagner KD. The role of PPARs in disease. Cells 2020; 9:23-67. 6. Wu CW, Yu J, Sung JJ. Peroxisome proliferator-activated receptor delta and gastric cancer (Review). Oncol Rep 2009; 22:451-457. 7. Régnier M, Polizzi A, Smati S, Lukowicz C, Fougerat A, Lippi Y, et al. Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity. Sci Rep 2020; 10:64-89. 8. Wagner N, Wagner KD. PPAR beta/delta and the hallmarks of cancer. Cells 2020; 9:1133-1140. 9. Chen L, Li L, Chen J, Li L, Zheng Z, Ren J, Qiu Y. Oleoylethanolamide, an endogenous PPAR-α ligand, attenuates liver fibrosis targeting hepatic stellate cells. Oncotarget 2015; 6:42530-42540. 10. Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol 2015; 62:720-733. 11. Fhu CW, Ali A. Fatty acid synthase: An emerging target in cancer. Molecules 2020; 25:39-35. 12. Ferré P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res 2007; 68:72-82. 13. Wilentz RE, Witters LA, Pizer ES. Lipogenic enzymes fatty acid synthase and acetyl-coenzyme A carboxylase are coexpressed with sterol regulatory element binding protein and Ki-67 in fetal tissues. Pediatr Dev Pathol 2000; 3:525-531. 14. Song S, Attia RR, Connaughton S, Niesen MI, Ness GC, Elam MB, et al. Peroxisome proliferator activated receptor alpha (PPARalpha) and PPAR gamma coactivator (PGC-1alpha) induce carnitine palmitoyltransferase IA (CPT-1A) via independent gene elements. Mol Cell Endocrinol 2010; 325:54-63. 15. Shakerian E, Akbari R, Mohammadtaghvaei N, Gahrooie MM, Afarin R. Quercetin reduces hepatic fibrogenesis by inhibiting tgf-β/smad3 signaling pathway in LX-2 cell line. Jundishapur J Nat Pharm Prod 2022; 17-27. 16. Shakerian E, Afarin R, Akbari R, Mohammadtaghvaei N. Effect of quercetin on the fructose-activated human hepatic stellate cells, LX-2, an in-vitro study. Mol Biol Rep 2022; 49:28-39. 17. Huwait E, Mobashir M. Potential and therapeutic roles of diosmin in human diseases. Biomedicines 2022; 10:1076-1090. 18. Zou Y, Li J, Lu C, Wang J, Ge J, Huang Y, Zhang L, et al. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life Sci 2006; 79:1100-1107. 19. Wang N, Kong R, Luo H, Xu X, Lu J. Peroxisome proliferator-activated receptors associated with nonalcoholic fatty liver disease. PPAR Res 2017; 2017:6561701. 20. Pan J, Zhou W, Xu R, Xing L, Ji G, Dang Y. Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease. Biomed Pharmacother 2022; 151:113-127. 21. Akbari R, Behdarvand T, Afarin R, Yaghooti H, Jalali MT, Mohammadtaghvaei N. Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis. BMC Pharmacol Toxicol 2021; 22:53-60. 22. Roy S, Ghosh A. Significant reduction of elevated triglycerides and liver fibrosis in diabetic dyslipidemia with saroglitazar: A case report. Cureus 2019; 11: e6361. 23. Kumar D, Goand UK, Gupta S, Shankar K, Varshney S, Rajan S, et al. Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue. Eur J Pharmacol 2018; 822:32-42. 24. Ali FEM, Sayed AM, El-Bahrawy AH, Omar ZMM, Hassanein EHM. Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against gentamicin-induced nephrotoxicity. Life Sci 2021; 275:119349. 25. Hasan HF, Abdel-Rafei MK, Galal SM. Diosmin attenuates radiation-induced hepatic fibrosis by boosting PPAR-γ expression and hampering miR-17-5p-activated canonical Wnt-β-catenin signaling. Biochem Cell Biol 2017; 95:400-414. 26. Gu H, An HJ, Gwon MG, Bae S, Zouboulis CC, Park KK. The effects of synthetic srebp-1 and ppar-γ decoy oligodeoxynucleotide on acne-like disease in vivo and in vitro via lipogenic regulation. Biomolecules 2022; 12:1858. 27. Gawrieh S, Noureddin M, Loo N, Mohseni R, Awasty V, Cusi K, et al. Saroglitazar, a PPAR-α/γ agonist, for treatment of NAFLD: A randomized controlled double-blind phase 2 trial. Hepatology 2021; 74:1809-1824. 28. Hong F, Pan S, Guo Y, Xu P, Zhai Y. PPARs as nuclear receptors for nutrient and energy metabolism. Molecules 2019; 24:25-45. 29. Boeckmans J, Natale A, Rombaut M, Buyl K, Rogiers V, De Kock J, et al. Anti-NASH drug development hitches a lift on PPAR agonism. Cells 2019; 9:37-40. 30. Dutta D, Bhattacharya S, Surana V, Aggarwal S, Singla R, Khandelwal D, et al. Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis. Diabetes Metab Syndr 2020; 14:1759-1768. 31. Abdel-Reheim MA, Messiha BA, Abo-Saif AA. Hepatoprotective effect of diosmin on iron-induced liver damage. Int J Pharmacol 2017; 13:529-540. 32. Tahir M, Rehman MU, Lateef A, Khan R, Khan AQ, Qamar W, et al. Diosmin protects against ethanol-induced hepatic injury via alleviation of inflammation and regulation of TNF-α and NF-κB activation. Alcohol 2013; 47:131-139. 33. Ali FEM, Azouz AA, Bakr AG, Abo-Youssef AM, Hemeida RAM. Hepatoprotective effects of diosmin and/or sildenafil against cholestatic liver cirrhosis: The role of Keap-1/Nrf-2 and P38-MAPK/NF-κB/iNOS signaling pathway. Food Chem Toxicol 2018; 120:294-304. | ||
|
آمار تعداد مشاهده مقاله: 618 تعداد دریافت فایل اصل مقاله: 457 |
||